Cardiotoxicity and myocardial infarction‐associated DNA damage induced by thiamethoxam in vitro and in vivo: Protective role of Trigonella foenum‐graecum seed‐derived polysaccharide

Abstract

The risk of pesticides on the human health and environment has drawn increasing attention. Today, new tools are developed to reduce pesticide adverse effects. This study aimed to evaluate the toxicity induced by, thiamethoxam (TMX), and the cytoprotective effect of a novel polysaccharide, named fenugreek seed water polysaccharide (FWEP) in vitro using H9c2 cardiomyoblastes and in vivo using Wistar rat model. Animals were assigned into four groups per eight rats each: group 1 served as a control group, group 2 received TMX, group 3, and group 4 received both FWEP and TMX tested at two doses (100 and 200 mg/kg, respectively). Regarding the in vitro study, our results demonstrated that TMX induced a decrease in H9c2 cell viability up to 70% with the highest concentration. In vivo, TMX injection induced marked heart damage noted by a significant increase in plasma lactate dehydrogenase, creatine phosphokinase, troponin-T, aspartate amino transferase activities, cholesterol, and triglyceride levels. Concomitant alterations in cardiac antioxidant defense system revealed depletion in the levels of glutathione and non-protein thiol and an increase in the activity of superoxide dismutase, catalase, and glutathione peroxidase. Similarly, a significant increase in heart lipid, malondialdehyde, advanced oxidation protein product and in protein carbonyls levels was also noted. In addition, heart tissues histo-architecture displayed major presence of apoptosis and necrosis as confirmed by DNA degradation. However, supplementation with FWEP alleviated heart oxidative damage and genotoxicity. In this manner, ABTS radical-scavenging activity, linoleic acid oxidation tests and heart genomic and DNA nicking assay had proved FWEP strong antioxidant potential. In conclusion, FWEP provided significant protection against TMX-induced heart injury, and could be a useful and efficient agent against cardiotoxicity and atherosclerosis. K E Y W O R D S cardiotoxicity, cytotoxicity, oxidative stress, polysaccharide, thiamethoxam

Protective Effect of Polysaccharides Extracted from Cudrania tricuspidata Fruit against Cisplatin-Induced Cytotoxicity in Macrophages and a Mouse Model

“…Second, as demonstrated in recent studies showing the molecular mechanisms of the apoptotic death in cancer [ 33 , 34 , 35 ], the cytoprotective action of CTPS was mediated via suppressing the cisp-induced apoptotic pathways such as the upregulation of Bax, cytosolic cytochrome c , PARP cleavage, caspase-3, -8, and -9, and the downregulation of Bcl-2. These findings are consistent with those from earlier studies that reported the cytoprotective effects of polysaccharides derived from natural products in apoptotic cell death [ 36 , 37 , 38 ]. To further identify the mediators responsible for the cytoprotective action of CTPS on cisp-treated macrophages, we showed that CTPS suppressed the cisp-induced apoptotic pathways via reducing ROS production and MTP loss.…”

An Evaluation of Traditional Persian Medicine for the Management of SARS-CoV-2

“…Furthermore, trigonelline could reduce the level of heat shock protein (HSP)-27 and aBcrystallin, two novel biomarkers of oxidative damage, in the myocardium damage, further confirming the cardioprotective activity of fenugreek (Panda et al, 2013). Polysaccharides as another important category of fenugreek components have demonstrated significant cardioprotective activity both in vitro and in vivo, possibly due to their antioxidant activity and prevention of DNA damage (Feki et al, 2019). Aside from antioxidant activity (Tripathi and Chandra, 2009), inhibition of pathologic NO production by inducible nitric oxide synthase (iNOS) and markers of cardiac fibrosis, such as fibronectin and collagen, seem to be the main cardioprotective mechanisms of fenugreek demonstrated in streptozotocin (STZ)-induced cardiac damage (Pradeep and Srinivasan, 2018).…”

Recent Progress in Environmental Toxins-Induced Cardiotoxicity and Protective Potential of Natural Products

“…The antioxidant activity of polyphenols depends on their ability to scavenge free radicals, donate hydrogen atoms or electrons, or chelate metal cations, and the structure is a key determinant of their free radical scavenging and metal chelating activity (Yordi et al, 2012). However, due to Feki et al (2019) low bioavailability and kinetic limitations, the direct antioxidant activity of polyphenols seems to be insufficient in the body. As Visioli et al reported, the concentrations of polyphenols used in in-vitro studies usually range from μmol/L to mmol/L, while plasma metabolite concentrations rarely exceed nmol/L after normal dietary intake (Visioli et al, 2011).…”

“…Feki et al extracted a polysaccharide from fenugreek seeds, called fenugreek seed water polysaccharide. Administration of this polysaccharide to thiamethoxam-treated rats shows a strong protective effect on the oxidative stress of the heart, which is manifested in the significant improvement of enzymatic and non-enzymatic antioxidants and the restoration of histopathological changes in the heart tissue ( Feki et al, 2019 ). Fenugreek seed water polysaccharide owns a great cardioprotective potential, but its specific mechanism needs to be further elucidated.…”